Discovery of Benzamide Analogues as a Novel Class of 5-HT3 Receptor Agonists

✍ Scribed by Dr. Charlotte G. Jørgensen; Dr. Bente Frølund; Dr. Jan Kehler; Dr. Anders A. Jensen

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 328 KB
• Volume: 6
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.201000444

✦ Synopsis

Abstract

A 5‐HT~3~ receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5‐HT~3~A receptor yielded substantial information concerning the analogues as 5‐HT~3~ receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5‐HT~3~ receptor agonist, as it does not possess a positively charged functionality, which is essential for the binding of all orthosteric ligands to the receptor. Preliminary investigations suggest that the compounds may exert their effects on 5‐HT~3~ receptors by binding to an allosteric site in the receptor complex.